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Nerve growth factor attenuates oxidant‐induced β‐amyloid neurotoxicity in sporadic Alzheimer’s disease cybrids
Author(s) -
Onyango Isaac G.,
Ahn JinYoung,
Tuttle Jeremy B.,
Bennett Jr James P.,
Swerdlow Russell H.
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06871.x
Subject(s) - neurotoxicity , biology , signal transduction , microbiology and biotechnology , nerve growth factor , tropomyosin receptor kinase a , kinase , receptor , endocrinology , medicine , genetics , toxicity
J. Neurochem. (2010) 114 , 1605–1618. Abstract Although mitochondrial dysfunction has been linked to Alzheimer’s disease (AD), it is not fully understood how this dysfunction may induce neuronal death. In this study, we show that transmitochondrial hybrid cells (cybrids) expressing mitochondrial genes from patients with sporadic AD (SAD) have substantial alterations in basal upstream tyrosine kinase signaling and downstream serine‐threonine kinase signaling that are mediated by intracellular free radicals. This is associated with reduced tropomyocin receptor kinase (TrkA) and p75 neurotrophin receptor receptor expression that profoundly alters nerve growth factor signaling, increases generation of Aβ and decreases viability. Many of these observed effects in SAD cybrids would be predicted to increase risk of premature neuronal death and reduce resistance to stressors and add further support for the pathogenic role of mtDNA expression in the pathogenesis of SAD.

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